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RU2018115715A - STABILIZING PHARMACEUTICAL COMPOSITIONS CAMPTOTECINE - Google Patents

STABILIZING PHARMACEUTICAL COMPOSITIONS CAMPTOTECINE Download PDF

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RU2018115715A
RU2018115715A RU2018115715A RU2018115715A RU2018115715A RU 2018115715 A RU2018115715 A RU 2018115715A RU 2018115715 A RU2018115715 A RU 2018115715A RU 2018115715 A RU2018115715 A RU 2018115715A RU 2018115715 A RU2018115715 A RU 2018115715A
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irinotecan
liposomes
composition
liposomal
sos
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RU2018115715A
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RU2018115715A3 (en
RU2732567C2 (en
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Дэрил С. ДРАММОНД
Дмитри Б. КИРПОТИН
Марк Имон ХАЙЕС
Чарльз НОБЛ
Кевин КЕСПЕР
Энтоин М. ЭВЭД
Дуглас Дж. МУР
Эндрю Дж. О'Брайен
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Ипсен Биофарм Лтд.
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Claims (45)

1. Стабилизированная для хранения липосомальная композиция иринотекана, имеющая рН 7,00-7,50 и содержащая дисперсию липосом иринотекана, инкапсулирующих иринотекана сахарозы октасульфат в везикулах, состоящих из холестерина и фосфолипидов 1,2-дистеароил-sn-глицеро-3-фосфохолина (ДСФХ) и метокси-терминированного полиэтиленгликоля (MW 2000)-дистеароилфосфатидилэтаноламина (МПЭГ-2000-ДСФЭ), при концентрации фрагмента иринотекана, эквивалентной в граммах безводного свободного основания иринотекана, 500 мг (±10%) фрагмента иринотекана на ммоль общего количества липосомного фосфолипида и 4,3 мг фрагмента иринотекана на мл липосомальной композиции иринотекана, стабилизированной для хранения липосомальной композиции иринотекана, стабилизированной с образованием менее 20 мол.% лизо-ФХ в течение первых 6 месяцев хранения при 4°C.1. Storage-stabilized liposome composition of irinotecan, having a pH of 7.00-7.50 and containing a dispersion of liposomes of irinotecan, encapsulating sucrose octin sulfate irinotecan in vesicles consisting of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine phospholipids ( DSPC) and methoxy-terminated polyethylene glycol (MW 2000) -distearoylphosphatidylethanolamine (MPEG-2000-DSPE), at a concentration of an irinotecan fragment equivalent in grams of anhydrous free base of irinotecan, 500 mg (± 10%) of an irinotecan fragment per mmole of total t he liposomal phospholipid and 4.3 mg per mL fragment irinotecan liposome composition irinotecan stabilized for storage irinotecan liposome composition stabilized to form at least 20 mol.% lyso-PC in the first 6 months of storage at 4 ° C. 2. Стабилизированная для хранения липосомальная композиция иринотекана, имеющая рН 7,00-7,50 и содержащая дисперсию липосом иринотекана, инкапсулирующих иринотекана сахарозы октасульфат в моноламеллярных бислойных везикулах, состоящих из холестерина и фосфолипидов 1,2-дистеароил-sn-глицеро-3-фосфохолина (ДСФХ) и метокси-терминированного полиэтиленгликоля (MW 2000)-дистеароилфосфатидилэтаноламина (МПЭГ-2000-ДСФЭ), при концентрации фрагмента иринотекана, эквивалентной в граммах безводного свободного основания иринотекана, 500 мг (±10%) фрагмента иринотекана на ммоль общего количества липосомного фосфолипида и 4,3 мг фрагмента иринотекана на мл липосомальной композиции иринотекана, стабилизированной для хранения липосомальной композиции иринотекана, имеющей грамм-эквивалентное соотношение иринотекана/соединения сульфата, равное 0,85-1,2.2. Storage-stabilized liposome composition of irinotecan, having a pH of 7.00-7.50 and containing a dispersion of liposomes of irinotecan, encapsulating sucrose irinotecan, octasulfate in monolamellar bilayer vesicles consisting of cholesterol and 1,2-distearoyl-3-gly-phospholipids phosphocholine (DPC) and methoxy-terminated polyethylene glycol (MW 2000) -distearoylphosphatidylethanolamine (MPEG-2000-DSFE), at a concentration of an irinotecan fragment equivalent in grams of anhydrous free base of irinotecan, 500 mg (± 10%) of an iririte fragment mmol swells on the total amount of liposome phospholipid and 4.3 mg of irinotecan fragment per ml of liposomal irinotecan composition stabilized for storage irinotecan liposome composition having a gram-equivalent ratio of irinotecan / sulfate compounds equal 0,85-1,2. 3. Стабилизированная для хранения липосомальная композиция иринотекана, стабилизированная с образованием менее 20 мол.% лизо-ФХ в течение первых 6 месяцев хранения при 4°C, липосомальная композиция иринотекана, полученная с помощью способа, включающего стадии:3. Storage-stabilized liposome composition of irinotecan, stabilized with the formation of less than 20 mol.% Lyso-FC during the first 6 months of storage at 4 ° C, liposome composition of irinotecan obtained using a method comprising the steps of: (а) образование липидной дисперсии в растворе, полученном из ТЭА8SOS и/или ДЭА8SOS, имеющем концентрацию сульфата от 0,4 до 0,5 М и рН от 5 до 7, причем липиды в указанной дисперсии представляют собой ДСФХ, холестерин и МПЭГ-2000-ДСФЭ в молярном соотношении приблизительно 3:2:0,015, соответственно;(a) the formation of a lipid dispersion in a solution obtained from TEA 8 SOS and / or DEA 8 SOS having a sulfate concentration of from 0.4 to 0.5 M and a pH of 5 to 7, the lipids in this dispersion being DSPC, cholesterol and MPEG-2000-DSFE in a molar ratio of approximately 3: 2: 0.015, respectively; (b) экструзия липидной дисперсии от 60 до 70°С, по меньшей мере, через одну мембрану 0,1 мкм для образования липосом;(b) extruding the lipid dispersion from 60 to 70 ° C. through at least one 0.1 μm membrane to form liposomes; (c) по существу удаление ионов, полученных из ТЭА8SOS и/или ДЭА8SOS, которые находятся за пределами липосом;(c) essentially removing ions derived from TEA 8 SOS and / or DEA 8 SOS that are outside the liposomes; (d) взаимодействие липосом при температуре от 60 до 70°С с раствором, полученным с использованием свободного основания иринотекана или соли иринотекана, таким образом получение препарата липосом, инкапсулирующих иринотекан;(d) the interaction of liposomes at a temperature of from 60 to 70 ° C with a solution obtained using the free base of irinotecan or a salt of irinotecan, thus obtaining a preparation of liposomes encapsulating irinotecan; (e) по существу удаление веществ, полученных из ингредиентов ТЭА8SOS и/или ДЭА8SOS и иринотекана, которые находятся за пределами липосом; и(e) essentially removing substances derived from the ingredients of TEA 8 SOS and / or DEA 8 SOS and irinotecan that are outside the liposomes; and (f) установление рН композиции от 7,0 до 7,5.(f) setting the pH of the composition from 7.0 to 7.5. 4. Липосомальная композиция иринотекана по любому одному из пп.1-3, полученная с помощью способа, включающего стадии:4. The liposomal composition of irinotecan according to any one of claims 1 to 3, obtained using a method comprising the steps of: (а) образование липидной дисперсии в растворе, полученном из ТЭА8SOS, имеющем концентрацию сульфата от 0,4 до 0,5 М и рН от 5 до 7, причем липиды в указанной дисперсии представляют собой ДСФХ, холестерин и МПЭГ-2000-ДСФЭ в молярном соотношении приблизительно 3:2:0,015, соответственно;(a) the formation of a lipid dispersion in a solution obtained from TEA 8 SOS having a sulfate concentration of from 0.4 to 0.5 M and a pH of 5 to 7, the lipids in this dispersion being DSPH, cholesterol and MPEG-2000-DSPE in a molar ratio of approximately 3: 2: 0.015, respectively; (b) экструзия липидной дисперсии от 60 до 70°С, по меньшей мере, через одну мембрану 0,1 мкм для образования липосом;(b) extruding the lipid dispersion from 60 to 70 ° C. through at least one 0.1 μm membrane to form liposomes; (c) по существу удаление ионов, полученных из ТЭА8SOS, которые находятся за пределами липосом;(c) essentially removing ions derived from TEA 8 SOS that are outside the liposomes; (d) взаимодействие липосом при температуре от 60 до 70°С с раствором, полученным с использованием свободного основания иринотекана или соли иринотекана, таким образом получение препарата липосом, инкапсулирующих иринотекан;(d) the interaction of liposomes at a temperature of from 60 to 70 ° C with a solution obtained using the free base of irinotecan or a salt of irinotecan, thus obtaining a preparation of liposomes encapsulating irinotecan; (e) по существу удаление веществ, полученных из ингредиентов ТЭА8SOS и иринотекана, которые находятся за пределами липосом; и(e) essentially removing substances derived from the ingredients of TEA 8 SOS and irinotecan that are outside the liposomes; and (f) установление рН композиции от 7,0 до 7,5.(f) setting the pH of the composition from 7.0 to 7.5. 5. Липосомальная композиция иринотекана по п.4, в которой липидная дисперсия экструдируется через, по меньшей мере, две многослойные поликарбонатные мембраны 0,1 мкм.5. The liposomal irinotecan composition according to claim 4, in which the lipid dispersion is extruded through at least two multilayer polycarbonate membranes of 0.1 μm. 6. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, в которой липосомы имеют средний размер 110 нм, как определено с помощью динамического рассеяния света, и в которой размер определяется методом кумулянтов.6. The liposome composition of irinotecan according to any one of the preceding paragraphs, in which the liposomes have an average size of 110 nm, as determined by dynamic light scattering, and in which the size is determined by the cumulant method. 7. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, имеющая общее содержание фрагмента иринотекана, эквивалентное 4,3 мг/мл безводного свободного основания иринотекана.7. The liposomal composition of irinotecan according to any one of the preceding paragraphs, having a total content of irinotecan fragment equivalent to 4.3 mg / ml of anhydrous free base of irinotecan. 8. Липосомальная композиция иринотекана по любому одному из пп.3-6, в которой:8. The liposomal composition of irinotecan according to any one of claims 3 to 6, in which: на стадии (а) липосомы образуются из ТЭА8SOS, имеющего концентрацию сульфата от 0,43 до 0,47 М; иat the stage (a), the liposomes are formed from TEA 8 SOS having a sulfate concentration of from 0.43 to 0.47 M; and на стадии (d) раствор, полученный с использованием свободного основания иринотекана или соли иринотекана, имеет содержание фрагмента иринотекана, эквивалентное 500 г (±10%) безводного свободного основания иринотекана на моль ДСФХ; иin step (d), the solution obtained using the free base of irinotecan or the salt of irinotecan has an irinotecan fragment content equivalent to 500 g (± 10%) of the anhydrous free base of irinotecan per mole of DPC; and на стадии (f) установление рН композиции от 7,2 до 7,3.in step (f), adjusting the pH of the composition from 7.2 to 7.3. 9. Липосомальная композиция по любому одному из предшествующих пунктов, содержащая менее 1 мол.% лизофосфатидилхолина (лизо-ФХ) до хранения при приблизительно 4°С и 20 мол.% или менее (по отношению к общему количеству липосомного фосфолипида) лизо-ФХ после 180 дней хранения при приблизительно 4°С.9. The liposomal composition according to any one of the preceding paragraphs, containing less than 1 mol.% Lysophosphatidylcholine (lyso-PX) before storage at approximately 4 ° C and 20 mol.% Or less (relative to the total amount of liposomal phospholipid) lyso-PX after 180 days storage at approximately 4 ° C. 10. Липосомальная композиция по п.9, содержащая 20 мол.% или менее (по отношению к общему количеству липосомного фосфолипида) лизофосфатидилхолина (лизо-ФХ) после 6, 9 или 12 месяцев хранения при приблизительно 4°С.10. The liposome composition according to claim 9, containing 20 mol% or less (relative to the total amount of liposome phospholipid) of lysophosphatidylcholine (lyso-FC) after 6, 9 or 12 months of storage at about 4 ° C. 11. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, содержащая в общей сложности от 6,1 до 7,5 мг ДСФХ/мл, от 2 до 2,4 мг холестерина/мл и от 0,11 до 0,13 мг МПЭГ-2000-ДСФЭ/мл, все в водном изотоническом буфере.11. The liposome composition of irinotecan according to any one of the preceding paragraphs, containing a total of 6.1 to 7.5 mg DSPC / ml, 2 to 2.4 mg cholesterol / ml and 0.11 to 0.13 mg MPEG -2000-DSFE / ml, all in aqueous isotonic buffer. 12. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, в которой липосомальный иринотекан содержит липосомы иринотекана в изотоническом водном буфере HEPES в концентрации от 2 до 20 мМ.12. The liposomal irinotecan composition according to any one of the preceding claims, wherein the liposomal irinotecan contains irinotecan liposomes in isotonic HEPES aqueous buffer at a concentration of from 2 to 20 mM. 13. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, дополнительно содержащая хлорид натрия в концентрации от 130 до 160 мМ.13. The liposome composition of irinotecan according to any one of the preceding paragraphs, optionally containing sodium chloride in a concentration of from 130 to 160 mm. 14. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, в которой иринотекан, инкапсулированный в липосомы, находится в гелеобразном или осажденном состоянии в виде соли октасульфата сахарозы.14. The liposomal irinotecan composition according to any one of the preceding claims, wherein the irinotecan encapsulated in liposomes is in a gel or precipitated state in the form of a sucrose octasulfate salt. 15. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, в которой липосомы иринотекана имеют диаметр 95-115 нм, как измерено с помощью квазиупругого рассеяния света.15. The liposome composition of irinotecan according to any one of the preceding paragraphs, in which the liposomes of irinotecan have a diameter of 95-115 nm, as measured by quasi-elastic light scattering. 16. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, содержащая в общей сложности 6,81 мг ДСФХ/мл, 2,22 мг холестерина/мл и 0,12 мг МПЭГ-2000-ДСФЭ/мл, 4,05 мг/мл водного буфера HEPES и 8,42 мг хлорида натрия/мл.16. The liposomal composition of irinotecan according to any one of the preceding paragraphs, containing a total of 6.81 mg of DPPC / ml, 2.22 mg of cholesterol / ml and 0.12 mg of MPEG-2000-DSFE / ml, 4.05 mg / ml HEPES aqueous buffer and 8.42 mg sodium chloride / ml. 17. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, имеющая рН 7,25, в которой липосомы иринотекана имеют диаметр 110 нм, как измерено с помощью квазиупругого рассеяния света.17. The liposome composition of irinotecan according to any one of the preceding paragraphs, having a pH of 7.25, in which the liposomes of irinotecan have a diameter of 110 nm, as measured by quasi-elastic light scattering. 18. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, образующая менее 1 мг/мл лизо-фосфатидилхолина (лизо-ФХ) после 6 месяцев хранения при приблизительно 4°С.18. The liposome composition of irinotecan according to any one of the preceding paragraphs, forming less than 1 mg / ml of lysophosphatidylcholine (lyso-PX) after 6 months of storage at approximately 4 ° C. 19. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, полученная с помощью способа, включающего стадии:19. The liposomal composition of irinotecan according to any one of the preceding paragraphs, obtained using a method comprising the steps of: (а) образование липидной дисперсии в растворе ТЭА8SOS, имеющем концентрацию сульфата приблизительно 0,45 М и рН приблизительно 6,5, причем липиды в указанной дисперсии состоят из 1,2-дистеароил-sn-глицеро-3-фосфохолина (ДСФХ), холестерина и метокси-терминированного полиэтиленгликоля (MW 2000)-дистеароилфосфатидилэтаноламина (МПЭГ-2000-ДСФЭ) в молярном соотношении 3:2:0,015, соответственно;(a) the formation of a lipid dispersion in a TEA 8 SOS solution having a sulfate concentration of approximately 0.45 M and a pH of approximately 6.5, wherein the lipids in this dispersion are composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DPPC) , cholesterol and methoxy-terminated polyethylene glycol (MW 2000) -distearoylphosphatidylethanolamine (MPEG-2000-DSFE) in a molar ratio of 3: 2: 0.015, respectively; (b) экструзия липидной дисперсии от 60 до 70°С, по меньшей мере, через одну мембрану 0,1 мкм для образования липосом;(b) extruding the lipid dispersion from 60 to 70 ° C. through at least one 0.1 μm membrane to form liposomes; (c) удаление ионов, полученных из ТЭА8SOS, которые находятся за пределами липосом;(c) removing ions derived from TEA 8 SOS that are outside of the liposomes; (d) взаимодействие липосом при температуре от 60 до 70°С с раствором, полученным с использованием иринотекана гидрохлорида тригидрата, с получением препарата липосом, инкапсулирующих приблизительно 500 г (±10%) иринотекана на моль общего количества липосомного фосфолипида;(d) interaction of liposomes at a temperature of from 60 to 70 ° C with a solution obtained using irinotecan hydrochloride trihydrate to obtain a liposome preparation encapsulating approximately 500 g (± 10%) irinotecan per mole of the total amount of liposomal phospholipid; (e) удаление веществ, полученных из ингредиентов ТЭА8SOS и иринотекана, которые находятся за пределами липосом; и(e) removing substances derived from the ingredients of TEA 8 SOS and irinotecan that are outside of the liposomes; and (f) доведение рН композиции до приблизительно 7,3.(f) adjusting the pH of the composition to about 7.3. 20. Липосомальная композиция иринотекана по любому из предшествующих пунктов, содержащая в общей сложности менее 100 ч./млн. ТЭА.20. The liposomal composition of irinotecan according to any one of the preceding paragraphs, containing a total of less than 100 ppm. TEA. 21. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, содержащая в общей сложности 30-100 ч./млн. ТЭА или ДЭА.21. The liposomal composition of irinotecan according to any one of the preceding paragraphs, containing a total of 30-100 ppm. TEA or DEA. 22. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, в которой, по меньшей мере, 98% иринотекана инкапсулируют в липосомы иринотекана после 6 месяцев хранения при приблизительно 4°С.22. The liposome composition of irinotecan according to any one of the preceding claims, wherein at least 98% of irinotecan is encapsulated in the irinotecan liposomes after 6 months of storage at about 4 ° C. 23. Липосомальная композиция иринотекана по любому одному из предшествующих пунктов, содержащая композицию иринотекана формулы (I) в липосомах иринотекана, где х составляет 8:23. The liposome composition of irinotecan according to any one of the preceding paragraphs, containing the composition of irinotecan of the formula (I) in the liposomes of irinotecan, where x is 8:
Figure 00000001
(I)
Figure 00000001
(I)
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Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA86063C2 (en) * 2004-05-03 2009-03-25 Хермес Біосайенсез, Інк. Liposomes useful for drug delivery
AU2013202947B2 (en) 2012-06-13 2016-06-02 Ipsen Biopharm Ltd. Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan
US9717724B2 (en) 2012-06-13 2017-08-01 Ipsen Biopharm Ltd. Methods for treating pancreatic cancer using combination therapies
AU2015360761B2 (en) * 2014-12-09 2021-05-20 Ipsen Biopharm Ltd. Treatment of breast cancer with liposomal irinotecan
US11318131B2 (en) 2015-05-18 2022-05-03 Ipsen Biopharm Ltd. Nanoliposomal irinotecan for use in treating small cell lung cancer
MX381475B (en) 2015-08-20 2025-03-12 Ipsen Biopharm Ltd COMBINATION THERAPY USING LIPOSOMAL IRINOTECAN AND A POLY(ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR FOR THE TREATMENT OF CANCER.
TWI778942B (en) 2015-08-21 2022-10-01 英商益普生生物製藥有限公司 Methods for treating metastatic pancreatic cancer using combination therapies comprising liposomal irinotecan and oxaliplatin
US20170319573A1 (en) * 2015-10-16 2017-11-09 Ipsen Biopharm Ltd. Stabilizing Camptothecin Pharmaceutical Compositions
JP6941606B2 (en) 2015-10-16 2021-09-29 イプセン バイオファーム リミティド Stabilized camptothecin pharmaceutical composition
CN110402163A (en) 2016-11-02 2019-11-01 易普森生物制药有限公司 Use the combination therapy to treat gastric cancer for including liposome Irinotecan, oxaliplatin, 5 FU 5 fluorouracil (and formyl tetrahydrofolic acid)
JP7431419B2 (en) * 2018-11-14 2024-02-15 タイワン リポソーム カンパニー リミテッド Sustained-release pharmaceutical compositions containing therapeutic agents and uses thereof for treating diseases due to decreased bone density or cartilage loss
US20230219941A1 (en) 2020-06-18 2023-07-13 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and methods of use thereof
EP4169928A1 (en) 2021-10-25 2023-04-26 Sandoz Ag Process for the preparation of sucrose octasulfate octakistriethylammonium salt (tasos) powder and uses thereof
TW202434243A (en) * 2022-11-21 2024-09-01 日商富士軟片股份有限公司 Combination medicine containing liposome composition containing topotecan or its salt and DNA damage repair inhibitor
CN115808483A (en) * 2022-12-29 2023-03-17 上海研诺医药科技有限公司 A method for determining phospholipid-related substances in irinotecan hydrochloride liposome injection

Family Cites Families (158)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1408315A (en) 1972-11-13 1975-10-01 Sss Patents Ltd Toothed clutch
US4192869A (en) 1977-09-06 1980-03-11 Studiengesellschaft Kohle Mbh. Controlled improvement of the O2 release by intact erythrocytes with lipid vesicles
DE2740053A1 (en) 1977-09-06 1979-05-03 Klaus Prof Dr Med Gersonde USE OF ALLOSTERIC EFFECTORS WITH THE LIPID VESICLES WITH AN IRREVERSIBLE INCORPORATION FOR THE IMPROVED O DEEP 2 DISCHARGE OF THE HAEMOGLOBIN IN ERYTHROCYTES
US4397846A (en) 1981-05-15 1983-08-09 Murray Weiner Storage-stable lipid vesicles and method of preparation
US5059591B1 (en) 1983-05-26 2000-04-25 Liposome Co Inc Drug preparations of reduced toxicity
JPS6019790A (en) 1983-07-14 1985-01-31 Yakult Honsha Co Ltd Novel camptothecin derivative
IL72420A (en) 1983-07-22 1987-10-30 Hoffmann La Roche Aqueous vitamin e solutions and their manufacture
US5077056A (en) 1984-08-08 1991-12-31 The Liposome Company, Inc. Encapsulation of antineoplastic agents in liposomes
US5736155A (en) 1984-08-08 1998-04-07 The Liposome Company, Inc. Encapsulation of antineoplastic agents in liposomes
US4755388A (en) 1984-11-09 1988-07-05 The Regents Of The University Of California Liposome-encapsulated 5-fluoropyrimidines and methods for their use
DE3634392A1 (en) 1986-10-09 1988-04-14 Knoll Ag USE OF POLYSULFATED LOW MOLECULAR DEXTRANSULFATES
MX9203808A (en) 1987-03-05 1992-07-01 Liposome Co Inc HIGH DRUG CONTENT FORMULATIONS: LIPID, FROM LIPOSOMIC-ANTINEOPLASTIC AGENTS.
JPH0720857B2 (en) 1988-08-11 1995-03-08 テルモ株式会社 Liposome and its manufacturing method
US4990610A (en) 1988-08-25 1991-02-05 Applied Analytical Industries, Inc. Method for preparing high potency sucralfate
IL91664A (en) 1988-09-28 1993-05-13 Yissum Res Dev Co Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release
US5043165A (en) 1988-12-14 1991-08-27 Liposome Technology, Inc. Novel liposome composition for sustained release of steroidal drugs
US5043164A (en) 1989-01-17 1991-08-27 The University Of Tennessee Research Corporation Blood-stable, cholesterol-free liposomes
US4960790A (en) 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
US5618798A (en) 1989-04-20 1997-04-08 Bar-Shalom; Daniel Use of sucralfate to treat baldness
ZA902710B (en) 1989-05-22 1991-12-24 Univ Georgia Res Found Enzyme luminescence assay
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
PL296382A1 (en) 1991-02-02 1993-11-02 Nika Health Products Ltd Li Li Artificial membrane beads containing functionally active peptides responsible for fusion as a drug administering system
US5498420A (en) 1991-04-12 1996-03-12 Merz & Co. Gmbh & Co. Stable small particle liposome preparations, their production and use in topical cosmetic, and pharmaceutical compositions
JPH06511470A (en) 1991-07-03 1994-12-22 ネクスター・フアーマシユーテイカルズ・インコーポレイテツド Filling technology in the preparation of liposomes containing drugs
US5329213A (en) 1991-10-28 1994-07-12 Orton Kevin R Method of turning off the receiver of a radio controlled model
US5281237A (en) 1992-09-25 1994-01-25 Gimpelson Richard J Surgical stitching device and method of use
US5552156A (en) 1992-10-23 1996-09-03 Ohio State University Liposomal and micellular stabilization of camptothecin drugs
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
US6350853B1 (en) 1993-04-26 2002-02-26 Peter E. Nielsen Conjugated peptide nucleic acids having enhanced cellular uptake
DE4320597A1 (en) 1993-06-22 1995-01-05 Heinz C Prof Dr Dr Schroeder Use of polyphosphates for antiviral therapy and as immunomodulators
US6743917B2 (en) 1993-06-30 2004-06-01 University Of Pittsburgh Camptothecin analogs and methods of preparation thereof
US5994341A (en) 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
US5534241A (en) 1993-07-23 1996-07-09 Torchilin; Vladimir P. Amphipathic polychelating compounds and methods of use
US5538954A (en) 1994-06-24 1996-07-23 A/S Dumex (Dumex Ltd.) Salts of tetracyclines
GB9323588D0 (en) 1993-11-16 1994-01-05 Cortecs Ltd Hydrophobic preparation
PT744939E (en) 1994-02-04 2003-02-28 Lipocore Holding Ab PREPARATIONS IN BICAMADA PREPARED FROM DIGALACTOSILDIACYLIGICEROL CONTAINING GALACTOLIPIDO
US6312719B1 (en) 1994-03-04 2001-11-06 The University Of British Columbia Liposome compositions and methods for the treatment of atherosclerosis
US5783568A (en) 1994-06-10 1998-07-21 Sugen, Inc. Methods for treating cancer and other cell proliferative diseases
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5741516A (en) 1994-06-20 1998-04-21 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US6214388B1 (en) 1994-11-09 2001-04-10 The Regents Of The University Of California Immunoliposomes that optimize internalization into target cells
GB9424902D0 (en) 1994-12-09 1995-02-08 Cortecs Ltd Solubilisation Aids
WO1996025147A1 (en) 1995-02-14 1996-08-22 Sequus Pharmaceuticals, Inc. Liposome composition and method for administering liposome-loadable drugs
US5800833A (en) 1995-02-27 1998-09-01 University Of British Columbia Method for loading lipid vesicles
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
DE19605024A1 (en) 1996-01-31 1997-08-07 Schering Ag New selective taxanes, processes for their preparation and their pharmaceutical use
US5756475A (en) 1996-01-31 1998-05-26 Nisshin Flour Milling Co., Ltd. Isoprene derivatives
US6441025B2 (en) 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
CA2252055C (en) 1996-04-11 2007-01-16 The University Of British Columbia Fusogenic liposomes
US5997899A (en) 1996-10-01 1999-12-07 Skyepharma Inc. Method for producing liposomes with increased percent of compound encapsulated
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
WO1998017256A1 (en) 1996-10-22 1998-04-30 Dmitri Kirpotin Compound-loaded liposomes and methods for their preparation
US6210707B1 (en) 1996-11-12 2001-04-03 The Regents Of The University Of California Methods of forming protein-linked lipidic microparticles, and compositions thereof
US6143740A (en) 1996-11-19 2000-11-07 Georgetown University Heregulin antagonists and methods for their use
US5827533A (en) 1997-02-06 1998-10-27 Duke University Liposomes containing active agents aggregated with lipid surfactants
ATE359071T1 (en) 1997-05-15 2007-05-15 Univ Washington COMPOSITION AND METHOD FOR TREATING ALZHEIMER'S DISEASE AND OTHER AMYLOIDOSES
WO1999001110A1 (en) 1997-07-02 1999-01-14 Sdg, Inc. Targeted liposomal constructs for diagnostic and therapeutic uses
US6316612B1 (en) 1997-08-22 2001-11-13 Ribozyme Pharmaceuticals, Inc. Xylofuranosly-containing nucleoside phosphoramidites and polynucleotides
US6083923A (en) 1997-10-31 2000-07-04 Isis Pharmaceuticals Inc. Liposomal oligonucleotide compositions for modulating RAS gene expression
US6787132B1 (en) 1997-12-04 2004-09-07 Yissum Research Development Company Of The Hebrew University Of Jerusalem Combined chemo-immunotherapy with liposomal drugs and cytokines
US7244826B1 (en) 1998-04-24 2007-07-17 The Regents Of The University Of California Internalizing ERB2 antibodies
RU2130771C1 (en) 1998-06-01 1999-05-27 Автушенко Сергей Сергеевич Method of preparing liposomal preparations
US6726925B1 (en) 1998-06-18 2004-04-27 Duke University Temperature-sensitive liposomal formulation
US6200598B1 (en) 1998-06-18 2001-03-13 Duke University Temperature-sensitive liposomal formulation
GB9813100D0 (en) 1998-06-18 1998-08-19 Secr Defence Method of forming liposomes
AU1678900A (en) 1998-08-11 2000-03-06 All India Institute Of Medical Sciences A novel liposomal formulation useful in treatment of cancer and other proliferation diseases
ATE355827T1 (en) 1998-08-12 2007-03-15 Yissum Res Dev Co LIPOSOMAL THERAPEUTIC COMPOSITIONS PRODUCED BY AMMONIUM SULFATE GRADIENT
IL142573A0 (en) 1998-09-16 2002-03-10 Alza Corp Liposome-entrapped topoisomerase inhibitors
US6291676B1 (en) 1999-03-03 2001-09-18 University Of Kentucky Research Foundation Water-soluble derivatives of camptothecin/homocamptothecin
US7311924B2 (en) 1999-04-01 2007-12-25 Hana Biosciences, Inc. Compositions and methods for treating cancer
DK1176962T3 (en) 1999-04-29 2004-06-14 Alza Corp Liposome Compositions for Improved Drug Retention
US6720001B2 (en) 1999-10-18 2004-04-13 Lipocine, Inc. Emulsion compositions for polyfunctional active ingredients
US6511676B1 (en) 1999-11-05 2003-01-28 Teni Boulikas Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes
US20020049176A1 (en) 1999-11-10 2002-04-25 Anderson Christen M. Modulation of mitochondrial mass and function for the treatment of diseases and for target and drug discovery
EP1259225B1 (en) 2000-02-04 2006-10-04 Lipoxen Technologies Limited Process of dehydration/rehydration for making liposomes
US6545010B2 (en) 2000-03-17 2003-04-08 Aventis Pharma S.A. Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer
WO2001087306A2 (en) 2000-05-15 2001-11-22 Celgene Corp. Compositions and methods for the treatment of colorectal cancer
AU7038501A (en) 2000-06-30 2002-01-14 Inex Pharmaceuticals Corp Liposomal antineoplastic drugs and uses thereof
US6486320B2 (en) 2000-09-15 2002-11-26 Aventis Pharma S.A. Preparation of camptothecin and of its derivatives
WO2002036073A2 (en) 2000-11-02 2002-05-10 Smithkline Beecham Corporation Receptor antagonist-lipid conjugates and delivery vehicles containing same
US20030064948A1 (en) 2001-02-08 2003-04-03 Alfred Fahr Invasomes for therapy of disorders, their preparation and use
IL158160A0 (en) 2001-03-26 2004-03-28 Alza Corp Liposome composition for improved intracellular delivery of a therapeutic agent
US7219016B2 (en) 2001-04-20 2007-05-15 Yale University Systems and methods for automated analysis of cells and tissues
WO2003030864A1 (en) 2001-05-29 2003-04-17 Neopharm, Inc. Liposomal formulation of irinotecan
EP1432403B1 (en) 2001-10-03 2010-07-28 Celator Pharmaceuticals, Inc. Liposome loading with metal ions
US7850990B2 (en) 2001-10-03 2010-12-14 Celator Pharmaceuticals, Inc. Compositions for delivery of drug combinations
US20030129224A1 (en) 2001-11-13 2003-07-10 Paul Tardi Lipid carrier compositions and methods for improved drug retention
ES2387886T3 (en) 2001-11-13 2012-10-03 Celator Pharmaceuticals, Inc. Compositions that transport lipids with better blood stability
US20030220284A1 (en) 2002-02-22 2003-11-27 Patricia Yotnda Delivery of adenoviral DNA in a liposomal formulation for treatment of disease
WO2003092700A1 (en) 2002-04-29 2003-11-13 Gmp Oxycell, Inc. Inositol pyrophosphates, and methods of use thereof
CA2752143C (en) 2002-05-15 2014-09-23 Sutter West Bay Hospitals Delivery of nucleic acid-like compounds
AU2003245160B2 (en) 2002-06-28 2009-09-24 Arbutus Biopharma Corporation Method and apparatus for producing liposomes
US20040243101A1 (en) 2002-07-02 2004-12-02 Gillis Edward M. Minimally invasive drug delivery catheter
WO2004035032A2 (en) 2002-08-20 2004-04-29 Neopharm, Inc. Pharmaceutical formulations of camptothecine derivatives
AR036316A1 (en) 2002-08-29 2004-08-25 Monte Verde S A A PHARMACEUTICAL COMPOSITION OF SMALL SIZE LIPOSOMES AND PREPARATION METHOD
DE10242367A1 (en) 2002-09-12 2004-03-18 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Thermolabile liposomes with good stability in serum, e.g. for release of drugs or contrast agents in hyperthermic areas around tumors, formed from phosphatidyl choline(s) and phosphatidyl oligoglycerol
CA2506749A1 (en) 2002-11-26 2004-06-10 Gilead Sciences, Inc. Method of drug loading in liposomes by gradient
WO2005002546A1 (en) 2003-06-27 2005-01-13 Smithkline Beecham Corporation Stabilized topotecan liposomal composition and methods
AU2004264857B2 (en) 2003-07-09 2010-06-10 Sutter West Bay Hospitals Remote detection of substance delivery to cells
WO2005087196A1 (en) 2004-03-17 2005-09-22 Tokai University Educational System Drug delivery system based on immune response system
UA86063C2 (en) 2004-05-03 2009-03-25 Хермес Біосайенсез, Інк. Liposomes useful for drug delivery
US8658203B2 (en) 2004-05-03 2014-02-25 Merrimack Pharmaceuticals, Inc. Liposomes useful for drug delivery to the brain
AP2255A (en) 2004-06-01 2011-07-21 Yakult Honsha Kk Irinotecan preparation.
JP2008502690A (en) 2004-06-15 2008-01-31 アンドリュー シァン チェン， Phospholipid composition and methods for its preparation and use
PL2572661T3 (en) 2004-10-05 2020-06-01 Genzyme Corporation Stepped cannula
US20060129126A1 (en) 2004-11-19 2006-06-15 Kaplitt Michael G Infusion device and method for infusing material into the brain of a patient
US20060127467A1 (en) 2004-12-14 2006-06-15 Watkin Kenneth L Nanoparticles for delivery of therapeutic agents using ultrasound and associated methods
JP5243040B2 (en) 2004-12-21 2013-07-24 ムスク・ファウンデイション・フォー・リサーチ・ディベロップメント Compositions and methods for promoting wound healing and tissue regeneration
JP2006248978A (en) 2005-03-10 2006-09-21 Mebiopharm Co Ltd New liposome preparation
EP1951239A2 (en) 2005-10-25 2008-08-06 Celator Pharmaceuticals, Inc. Fixed ratio drug combination treatments for solid tumors
WO2007076117A2 (en) 2005-12-22 2007-07-05 Celator Pharmaceuticals, Inc. Liposomal formulations comprising secondary and tertiary amines and methods for preparing thereof
AU2007227466B2 (en) 2006-03-16 2011-11-17 Bionumerik Pharmaceuticals, Inc. Anti-cancer activity augmentation compounds and formulations and methods of use thereof
JP5199239B2 (en) 2006-04-20 2013-05-15 アムジエン・インコーポレーテツド Stable emulsion formulation
GB0614835D0 (en) 2006-07-26 2006-09-06 Isis Innovation Formation of bilayers of amphipathic molecules
ES2631727T3 (en) 2007-02-16 2017-09-04 Merrimack Pharmaceuticals, Inc. Antibodies against ErbB3 and their uses
WO2009097011A1 (en) 2007-08-17 2009-08-06 Celator Pharmaceuticals, Inc. Improved platinum drug formulations
WO2009040426A1 (en) 2007-09-28 2009-04-02 Universitätsspital Basel Immunoliposomes for treatment of cancer
WO2009059449A1 (en) 2007-11-05 2009-05-14 Celsion Corporation Novel thermosensitive liposomes containing therapeutic agents
US8067432B2 (en) 2008-03-31 2011-11-29 University Of Kentucky Research Foundation Liposomal, ring-opened camptothecins with prolonged, site-specific delivery of active drug to solid tumors
JP5639039B2 (en) 2008-04-11 2014-12-10 メリマック ファーマシューティカルズ インコーポレーティッド Human serum albumin linker and its conjugates
NZ588583A (en) 2008-04-15 2012-08-31 Protiva Biotherapeutics Inc Novel lipid formulations for nucleic acid delivery
US8852630B2 (en) 2008-05-13 2014-10-07 Yale University Chimeric small molecules for the recruitment of antibodies to cancer cells
US20110190623A1 (en) 2008-08-05 2011-08-04 The Methodist Hopsital Research Institute Thermally-activatable liposome compositions and methods for imaging, diagnosis and therapy
JP5677972B2 (en) 2008-11-18 2015-02-25 メリマック ファーマシューティカルズ インコーポレーティッド Human serum albumin linker and its conjugates
PL2508170T3 (en) 2009-12-03 2015-12-31 Jiangsu Hengrui Medicine Co Liposome of irinotecan or its hydrochloride and preparation method thereof
EP2394640A1 (en) 2010-05-21 2011-12-14 MediGene AG Improved liposomal formulations of lipophilic compounds
AU2011268101B2 (en) 2010-06-19 2014-09-25 Western University Of Health Sciences Novel formulation of pegylated-liposome encapsulated glycopeptide antibiotics
CN103327983A (en) 2010-12-06 2013-09-25 梅里麦克制药股份有限公司 Dosing and Administration to Prevent Cardiotoxicity in Treatment with ERBB2-Targeting Immunoliposomes Containing Anthracycline Chemotherapeutics
KR20140092226A (en) 2010-12-14 2014-07-23 테크니칼 유니버시티 오브 덴마크 Entrapment of radionuclides in nanoparticle compositions
CA2827118A1 (en) 2011-02-15 2012-08-23 Merrimack Pharmaceuticals, Inc. Compositions and methods for delivering nucleic acid to a cell
KR101517320B1 (en) 2011-04-19 2015-05-28 메리맥 파마슈티컬즈, 인크. Monospecific and bispecific anti-igf-1r and anti-erbb3 antibodies
US8691231B2 (en) 2011-06-03 2014-04-08 Merrimack Pharmaceuticals, Inc. Methods of treatment of tumors expressing predominantly high affinity EGFR ligands or tumors expressing predominantly low affinity EGFR ligands with monoclonal and oligoclonal anti-EGFR antibodies
AU2013249307B2 (en) 2012-04-17 2017-11-09 Merrimack Pharmaceuticals, Inc. Compositions and methods for non-invasive imaging
AU2013202947B2 (en) 2012-06-13 2016-06-02 Ipsen Biopharm Ltd. Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan
US9717724B2 (en) 2012-06-13 2017-08-01 Ipsen Biopharm Ltd. Methods for treating pancreatic cancer using combination therapies
EP2872219B1 (en) 2012-07-10 2017-09-06 Koninklijke Philips N.V. Release of molecules from container by selective heating of hair
US20140079773A1 (en) 2012-09-18 2014-03-20 Comfort Care For Animals Llc Encapsulating liposomes
AU2013374248A1 (en) 2012-12-14 2015-06-11 Merrimack Pharmaceuticals, Inc. Non-invasive imaging methods for patient selection for treatment with nanoparticulate therapeutic agents
EP3038600B1 (en) 2013-08-27 2020-06-03 Northeastern University Nanoparticle drug delivery system and method of treating cancer and neurotrauma
WO2015061592A1 (en) 2013-10-23 2015-04-30 Merrimack Pharmaceuticals, Inc. Liposomes for non-invasive imaging and drug delivery
US20150273060A1 (en) 2014-03-31 2015-10-01 Regents Of The University Of Minnesota Delivery compositions and methods
AU2015360761B2 (en) 2014-12-09 2021-05-20 Ipsen Biopharm Ltd. Treatment of breast cancer with liposomal irinotecan
TW201701880A (en) 2015-04-14 2017-01-16 莫瑞麥克製藥公司 Methods for improving the pharmacokinetics and therapeutic index of sustained release drug therapies
US11318131B2 (en) 2015-05-18 2022-05-03 Ipsen Biopharm Ltd. Nanoliposomal irinotecan for use in treating small cell lung cancer
EP4212148A1 (en) 2015-05-26 2023-07-19 Plumb Pharmaceuticals, Inc. Liposome loading
MX381475B (en) 2015-08-20 2025-03-12 Ipsen Biopharm Ltd COMBINATION THERAPY USING LIPOSOMAL IRINOTECAN AND A POLY(ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR FOR THE TREATMENT OF CANCER.
TWI778942B (en) 2015-08-21 2022-10-01 英商益普生生物製藥有限公司 Methods for treating metastatic pancreatic cancer using combination therapies comprising liposomal irinotecan and oxaliplatin
CA2999278A1 (en) 2015-09-21 2017-03-30 Mallinckrodt Llc Improved stability of liposome formulations and uses thereof
US20170319573A1 (en) 2015-10-16 2017-11-09 Ipsen Biopharm Ltd. Stabilizing Camptothecin Pharmaceutical Compositions
JP6941606B2 (en) * 2015-10-16 2021-09-29 イプセン バイオファーム リミティド Stabilized camptothecin pharmaceutical composition
US20180110771A1 (en) 2016-10-21 2018-04-26 Ipsen Biopharm Ltd. Liposomal Irinotecan Preparations
US20170202840A1 (en) 2016-01-14 2017-07-20 Merrimack Pharmaceuticals, Inc. Treatment of pancreatic cancer with liposomal irinotecan
US20170333421A1 (en) 2016-05-18 2017-11-23 Ipsen Biopharm Ltd. Population Pharmacokinetics of Liposomal Irinotecan
CA3023743A1 (en) 2016-05-18 2017-11-23 Ipsen Biopharm Ltd. Nanoliposomal irinotecan for use in treating small cell lung cancer
CN110402163A (en) 2016-11-02 2019-11-01 易普森生物制药有限公司 Use the combination therapy to treat gastric cancer for including liposome Irinotecan, oxaliplatin, 5 FU 5 fluorouracil (and formyl tetrahydrofolic acid)
US10772508B2 (en) 2017-11-22 2020-09-15 MediVisionTech Co., Ltd. Method for determining upper gastrointestinal bleeding course

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